13 replies to this topic

[Speculosity]

Hi everyone,

Okay, to keep this from being a wall of text, Someone I know took MDMA, and they have working memory problems now.

I learned through reading various studies that the main reason this problems occurs, is because MDMA significantly and (from what it says) almost irreversibly lowers the amount of the serotonin transporter (SERT), in the brain.

This correlates with why Bacopa temporarily increased my friend's memory while he was on it. Bacopa upregulates SERT.

Google's spitting out mild results, so I wanted to ask if anyone here knows how SERT is made (Might provide a clue/lead for increasing it), and if there is anyway to recover them to normal levels?

And if you don't know, or just know other ways to temporarily upregulate SERT, I'd love to see what you have to share if that's alright.

I'd really appreciate your help, thank you!

[Flex]

From my amateurish knowledge, it depends on the mechanism.

 

If You look into this as an example:

http://www.avensonli...JAP-01-0003.pdf

You´ll see that its PKC depend.

 

However its seemingly revrsible in this case.

 

Could You post some links about the irreversible downregulation ?

[OneScrewLoose]

You have it backwards. You don't want to upregulate SERT. SERT is known as the Serotonin Reuptake Transporter, and takes serotonin from the synapse, where it is active, and dumps it into the cells, where it is stored and (supposedly) inhert. The more SERT transporters, the less serotonin in the synapse. MDMA works by reversing the transporter, and dumping 5HT (Serotonin) from the cell, into the synapse.

What you want is less SERT activity. How long has it been since he took the MDMA? How long has he been on the Bacopa? Bacopa takes 8-12 weeks to take full effect. It (may) upregulate the density of certain serotonin receptors (the buttons 5HT work on), not SERT (the transporter that makes 5HT less available to work on those buttons).

 

Hope that helps.

[Speculosity]

From my amateurish knowledge, it depends on the mechanism.

 

If You look into this as an example:

http://www.avensonli...JAP-01-0003.pdf

You´ll see that its PKC depend.

 

However its seemingly revrsible in this case.

 

Could You post some links about the irreversible downregulation ?

 

 

You have it backwards. You don't want to upregulate SERT. SERT is known as the Serotonin Reuptake Transporter, and takes serotonin from the synapse, where it is active, and dumps it into the cells, where it is stored and (supposedly) inhert. The more SERT transporters, the less serotonin in the synapse. MDMA works by reversing the transporter, and dumping 5HT (Serotonin) from the cell, into the synapse.

What you want is less SERT activity. How long has it been since he took the MDMA? How long has he been on the Bacopa? Bacopa takes 8-12 weeks to take full effect. It (may) upregulate the density of certain serotonin receptors (the buttons 5HT work on), not SERT (the transporter that makes 5HT less available to work on those buttons).

 

Hope that helps.

 

Here is one study among many that say that MDMA lowers SERT.

 

http://www.ncbi.nlm....pubmed/18832433

 

"As compared with control values, SERT protein levels were markedly (-48% to -58%) reduced in striatum (caudate, putamen) and occipital cortex and less affected (-25%) in frontal and temporal cortices, whereas TPH protein was severely decreased in caudate and putamen (-68% and -95%, respectively)."

 

 

 

And here's evidence among many studies that says this impacts memory.

 

http://www.ncbi.nlm....les/PMC3419896/

 

"There are also extensive empirical data for impairments in memory and higher cognition, with the neurocognitive deficits correlating with the extent of SERT loss."

 

 

And lastly, bacopa DOES upregulate SERT, as said here, where it also says that it's one of the causes of its memory enhancing effects.

 

http://www.ncbi.nlm....pubmed/21129470

 

 

The bacopa actually worked for my friend in 2-3 days. But the problem was its effects were temporary. This is why I'd like to genuinely recover SERT, not just upregulate it. 

 

 

 

Flex,  thanks for the link, where inside it does it say it's reversible? I see that MDMA decreases it with PKC, but not how it can come back. Here's some evidence of it being long-lasting.

 

http://www.ncbi.nlm....les/PMC4058674/

 

"in addition, MDMA produces a long-lasting down-regulation of SERT gene expression; which, on the whole, has been used to invoke neuromodulatory mechanisms as an explanation to MDMA-induced 5-HT deficits."

[OneScrewLoose]

The real damage from MDMA has nothing to do with certain. MDMA allows reuptake of dopamine into serotonin cells. Normally DA isn't there. During an MDMA, in the 5HT cells, DA quickly gets broken down into things like quinines and hydrogen peroxide, which produces hydroxyl radicals. There are other oxidative radicals produced in this process, and the total amount of free-radicals in the brain goes up by 400%. This damages the serotoninergic cells. That's why it's imperative to take antioxidants, like R-Alpha Lipoic Acid, with MDMA. It really does make a difference.

I wouldn't pin the problem on SERT itself. There really is no evidence that it is specifically because of this over other possible damage to the 5HT system. I would approach it as a whole repair process. Try the combination of St. John's Wort (Perika brand), which upregulates 5HT receptors (takes about 5 weeks for full effect), and a quality Bacopa taken long-term which also can augument the 5HT system. Bacomind is the best and most-studied extract, but I can never find where to buy it. In it's place, I would recommend Nutrigold Bacopa.

[Flex]

Ok, this looks for an amateur like me quiet complicated i.e. how to tackle the ~65kDa band at the SERT promoter.

 

Anyway, heres what I´ve found:

Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region.

http://www.ncbi.nlm....pubmed/21647174

--> You can find Evodia Rutaecarpa when looking for the chinese name( called pin yin) = Wu Zhu Yu

I´ve tried it and it was for me rather medicore. The effects on SERT are perhaps transient, though I´m not sure.

 

When You have a rare disease or problem and cant find many informations, try to find the next more common diesase to gather more informations.

I would say that PSSD (post ssri sexual dysfunction) would fit somewhat in. However there are more laymans suggestions and experiences (e.g. Curcumin, meriva brand) than studies...

 

Natural 5-HT1A Agonists/Antagonists (PSSD,and Cognitive Function)

http://www.longecity...on/#entry722358

 

Search the longecity forum  or pssd forum for more infos. You will find that e.g. Coffee can inhibit reversibly tryptophan hydroxylase 2 (TPH2) so the one which is abudant in the brain or decrease exercise caused elevation at least.

 

For general recovery, You could look into nogo protein inhibition & etc:

 

Nogo-A inhibition and brain regrowth

http://www.longecity...rowth/?p=737252

 

Restoring critical period plasticity through deactivating axon growth inhibitor

http://www.longecity...or/#entry699582

Edited by Flex, 21 July 2015 - 09:38 PM.

[Speculosity]

Ok, this looks for an amateur like me quiet complicated i.e. how to tackle the ~65kDa band at the SERT promoter.

 

Anyway, heres what I´ve found:

Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region.

http://www.ncbi.nlm....pubmed/21647174

--> You can find Evodia Rutaecarpa when looking for the chinese name( called pin yin) = Wu Zhu Yu

I´ve tried it and it was for me rather medicore. The effects on SERT are perhaps transient, though I´m not sure.

 

When You have a rare disease or problem and cant find many informations, try to find the next more common diesase to gather more informations.

I would say that PSSD (post ssri sexual dysfunction) would fit somewhat in. However there are more laymans suggestions and experiences (e.g. Curcumin, meriva brand) than studies...

 

Natural 5-HT1A Agonists/Antagonists (PSSD,and Cognitive Function)

http://www.longecity...on/#entry722358

 

Search the longecity forum  or pssd forum for more infos. You will find that e.g. Coffee can inhibit reversibly tryptophan hydroxylase 2 (TPH2) so the one which is abudant in the brain or decrease exercise caused elevation at least.

 

For general recovery, You could look into nogo protein inhibition & etc:

 

Nogo-A inhibition and brain regrowth

http://www.longecity...rowth/?p=737252

 

Restoring critical period plasticity through deactivating axon growth inhibitor

http://www.longecity...or/#entry699582

 

 

Thanks a lot Flex!

 

I'm gonna look into Nogo, it looks interesting.

 

I learned that folic acid and its relatives also do the same thing.

[Speculosity]

The real damage from MDMA has nothing to do with certain. MDMA allows reuptake of dopamine into serotonin cells. Normally DA isn't there. During an MDMA, in the 5HT cells, DA quickly gets broken down into things like quinines and hydrogen peroxide, which produces hydroxyl radicals. There are other oxidative radicals produced in this process, and the total amount of free-radicals in the brain goes up by 400%. This damages the serotoninergic cells. That's why it's imperative to take antioxidants, like R-Alpha Lipoic Acid, with MDMA. It really does make a difference.

I wouldn't pin the problem on SERT itself. There really is no evidence that it is specifically because of this over other possible damage to the 5HT system. I would approach it as a whole repair process. Try the combination of St. John's Wort (Perika brand), which upregulates 5HT receptors (takes about 5 weeks for full effect), and a quality Bacopa taken long-term which also can augument the 5HT system. Bacomind is the best and most-studied extract, but I can never find where to buy it. In it's place, I would recommend Nutrigold Bacopa.

 

You're right, I just saw this study that could be the cause of the issues: http://www.mdma.net/...n/resprout.html

 

I also recently just found a study saying how even though people regained their axons, and SERT, they still had memory problems: http://www.ncbi.nlm....pubmed/16510479

 

St. John's wort and Bacopa have noticeable effects, but like I said, they go away as soon as it's ceased.

[Flex]

Thx,as well. Didnt know this about folic acid.

[gamesguru]

 

Bacopa extract displays strong serotonin receptor activity.

Researchers at the University of Montana have released results from a recent in vitro study on a standardized extract of Bacopa monnieri, a plant used widely and historically in the traditional Indian system of Ayurveda to enhance cognitive health, memory and mood. The results were presented at a poster session at the annual meeting of the American Society of Pharmacognosy held at Oregon State University in Corvallis, OR, in July. While previous in vitro studies on Bacopa focus on the neurotransmitters GABA and acetylcholine, this study provided direct evidence that Bacopa can also regulate the activity of specific serotonin receptors. The study concluded that the Bacopa extract displaces antagonist [3H] Ketanserin from serotonin receptor 5HT2a isolated from rats, and exhibited even stronger effects in its displacement of agonist 8-OH-DPAT from the 5HT1a receptor. The study also concluded that this Bacopa extract decreases cAMP production in cells with 5HT1a receptors, suggesting it causes an agonistic effect. This effect was similar to results from a previous study where Bacopa displayed antidepressant effects comparable to imipramine. Geni Herbs manufactured the Bacopa extract used in the study.

For further information: 317-776-3600.

 

http://www.thefreeli...ty.-a0139683595

Edited by gamesguru, 25 July 2015 - 04:18 PM.

[OneScrewLoose]

 

The real damage from MDMA has nothing to do with certain. MDMA allows reuptake of dopamine into serotonin cells. Normally DA isn't there. During an MDMA, in the 5HT cells, DA quickly gets broken down into things like quinines and hydrogen peroxide, which produces hydroxyl radicals. There are other oxidative radicals produced in this process, and the total amount of free-radicals in the brain goes up by 400%. This damages the serotoninergic cells. That's why it's imperative to take antioxidants, like R-Alpha Lipoic Acid, with MDMA. It really does make a difference.

I wouldn't pin the problem on SERT itself. There really is no evidence that it is specifically because of this over other possible damage to the 5HT system. I would approach it as a whole repair process. Try the combination of St. John's Wort (Perika brand), which upregulates 5HT receptors (takes about 5 weeks for full effect), and a quality Bacopa taken long-term which also can augument the 5HT system. Bacomind is the best and most-studied extract, but I can never find where to buy it. In it's place, I would recommend Nutrigold Bacopa.

 

You're right, I just saw this study that could be the cause of the issues: http://www.mdma.net/...n/resprout.html

 

I also recently just found a study saying how even though people regained their axons, and SERT, they still had memory problems: http://www.ncbi.nlm....pubmed/16510479

 

St. John's wort and Bacopa have noticeable effects, but like I said, they go away as soon as it's ceased.

 

That's only true if the person is only taking them for a year. After 1-3 years, there are significant neuronal changes that can be quite permenant.

[gamesguru]

Bacopa ... upregulate ... not SERT

ahem ...

Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation.  

RESULTS:

Oral administration of BMEE improved learning and retention of memory significantly in all behavioural tasks. Following BMEE treatment, the level of serotonin (5-HT) increased while dopamine (DA) decreased significantly. We also found variation in the level of acetylcholine (ACh). However, no significant changes were observed in the level of ACh and glutamate (Glu). The level of 5-HT was significantly elevated up to PND-37 and was then restored to normal level on PND-53. Interestingly, concomitant up-regulation was recorded in the mRNA expression of serotonin synthesizing enzyme tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) on PND-29 and PND-37, which was restored on PND-53.

CONCLUSIONS:

The results suggest that BMEE treatment significantly enhances the learning and retention of memory in postnatal rats possibly through regulating the expression of TPH2, 5-HT metabolism and transport.

 

 

 

Assorted studies:

Sonchus asper: brain antioxidant markers, cognitive performance and acetylcholinesterase activity of rats [similar to blueberries]

http://www.ncbi.nlm....les/PMC3527136/

 

Enhancement of Amygdaloid Neuronal Dendritic Arborization by Fresh Leaf Juice of Centella asiatica
http://www.hindawi.c...009/247831/abs/

Centella asiatica Leaf Extract Treatment During the Growth Spurt Period Enhances Hippocampal CA3 Neuronal Dendritic Arborization
http://www.hindawi.c...006/627102/abs/

Altered dendritic arborization of amygdala neurons in young adult rats orally intubated with Clitorea ternatea aqueous root extract
http://onlinelibrary...r.1657/abstract

 

Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats
http://www.scielo.br...ipt=sci_arttext

Enhanced dendritic arborization of amygdala neurons during growth spurt periods in rats orally intubated with Bacopa monniera extract
http://link.springer...2565-011-0104-z

 

--------

ß-adrenoceptor blockers increase cardiac sympathetic innervation by inhibiting autoreceptor suppression of axon growth

http://www.ncbi.nlm....pubmed/20844139

 

Retina-derived growth-promoting extract supports axonal regeneration in vivo
http://www.sciencedi...006899386908498

Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway
http://www.sciencema.../5903/963.short

Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein
http://www.nature.co...s/403439a0.html

Glial inhibition of CNS axon regeneration
http://www.nature.co...bs/nrn1956.html

A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration
http://www.sciencedi...896627394900426

Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors
http://www.nature.co...s/343269a0.html

Axon Regeneration in the Peripheral and Central Nervous Systems
http://www.ncbi.nlm....846285/#S2title

Berberine Promotes Axonal Regeneration in Injured Nerves of the Peripheral Nervous System
http://www.ncbi.nlm....les/PMC3308712/

Enhanced survival and regeneration of axotomized retinal ganglion cells by a mixture of herbal extracts
http://www.ncbi.nlm....pubmed/11939504

Growth-promoting activity of Hominis Placenta extract on regenerating sciatic nerve
http://www.ncbi.nlm....pubmed/16364210

Hedysari Extract Improves Regeneration after Peripheral Nerve Injury by Enhancing the Amplification Effect
http://journals.plos...al.pone.0067921

 

Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats.

http://www.ncbi.nlm....pubmed/24737429

 

Curcumin protects axons from degeneration in the setting of local neuroinflammation

http://www.ncbi.nlm....pubmed/24382451

 

Curcumin promotes nerve regeneration and functional recovery in rat model of nerve crush injury.

http://www.ncbi.nlm....pubmed/23669643

 

Low-Dose Curcumin Stimulates Proliferation, Migration and Phagocytic Activity of Olfactory Glial Cells

http://journals.plos...al.pone.0111787

 

Axonal Regeneration into Acellular Nerve Grafts Is Enhanced by Degradation of Chondroitin Sulfate Proteoglycan
http://www.jneurosci...6/6206.full.pdf

Genes Associated with Adult Axon Regeneration Promoted by Olfactory Ensheathing Cells: A New Role for Matrix Metalloproteinase 2
http://www.jneurosci...26/20/5347.full

Edited by gamesguru, 30 August 2015 - 05:10 PM.

[Flex]

wow cool !

Thanks for sharing

[kurdishfella]

should it not go to normal when you go off anything? Maybe not 100% but 99% , I guess depends how long you were on them and dosage etc

Edited by farshad, 18 December 2019 - 05:13 PM.